This invention relates to novel carbacyclin derivatives, processes for their production as well as their use as medicinal agents.
The precursor of carbacyclins, prostacyclin, was isolated in 1976 and clarified with respect to its structure in the same year (Prostaglandins 12: 915, 1976). For some time, the designation PGI.sub.2 has become accepted for prostacyclin, as a prostaglandin abbreviation. Correspondingly, carbacyclins are also called 6a-carbaprostaglandins I.sub.2.
The nomenclature of the compounds of this invention is based on a proposal by Morton and Brokaw (J. Org. Chem. 44: 2280[1979]). The synthesis of these compounds yields in all cases two double-bond isomers characterized by the symbols (5E) or (5Z). By substituting the top chain, for example, by an aromatic residue, structural formulae are obtained which can be described as follows: ##STR5##
Such prostacyclin analogs have been disclosed in DOS No. 3,146,278 and European Patent No. 0062 902.
Based on their biological and pharmacological properties, prostacyclins and their analogs are suitable for therapy and prophylaxis of thromboses, infarctions and other cardiovascular diseases. The duration of activity of these compounds is frequently still too brief for therapeutic purposes. For this reason, all structural modifications of known PGI.sub.2 derivatives aim at prolonging the period of efficacy, increasing the selectivity of activity, and simultaneously reducing the effective dose.